1. Technical Field
The present application relates generally to methods for modifying a substrate by exposing the substrate to a densified fluid under controlled conditions, in order to enhance selected properties of the substrate. More particularly, the application relates to method for modifying a polymer, or a metal alloy, by exposing the polymer or alloy to densified CO2 under subcritical and/or supercritical conditions, and impregnating the substrate with a drug compound.
2. Background Information
In the recent past, densified fluid technology has been the focus of numerous research and development studies based on the fundamentals of high-pressure phase behavior of materials. The technique has been well developed, both in fundamental understanding and numerous commercial applications since at least the late 1980s.
A densified fluid, as referred to herein, is a fluid maintained in the vicinity of the critical point of the fluid. Due to their liquid-like solvation power and gas-like mass transfer properties, these fluids are unique solvents for uses such as synthesis, extraction and separation. Processes utilizing such solvents may generally be carried out at moderate temperatures, thereby making the processes suitable for use with many heat-sensitive compounds, such as pharmaceutical drugs. In addition, the products resulting from such processes are generally free of residual solvents. This feature is particularly beneficial in, e.g., the pharmaceutical and medical device fields, due to strict limits on the residual solvent content of the resulting products.
The critical temperature of a compound is defined as the temperature above which the pure gaseous component cannot be liquefied regardless of the pressure applied, while the critical pressure is defined as the gas or vapor pressure at the corresponding critical temperature. The temperature and pressure at which the gas and liquid phases become indistinguishable is known as the critical point. If the conditions exceed the critical points, the densified fluid exists as a supercritical fluid (SCF). If either, or both, of the temperature and pressure of the fluid are slightly below the critical points, and the densified fluid remains in a fluid state and denser than a typical gas, the densified fluid exists in a state referred to herein as a subcritical fluid (SBCF). In some cases, a subcritical fluid is at about 95% or more of its critical temperature and/or 95% or more of its critical pressure. In other cases, either, or both, of the critical temperature and critical pressure may vary by a greater amount from the respective critical temperature or pressure of the fluid. A densified fluid as referred to herein may comprise a fluid existing as either a supercritical fluid or a subcritical fluid.
In the SCF region, the physical properties of a substance are remarkable and intermediate to both liquid and gas. Near the critical point of a fluid, changes in pressure or temperature may significantly alter the physical-chemical properties (e.g., density, diffusivity, or solubility characteristics) of the densified fluid. This can be particularly important in instances in which processing conditions are sensitively manipulated, such as in drug processing. Although many compounds are capable of existing as a SCF or a SBCF, carbon dioxide is a particularly attractive compound for such use. Carbon dioxide is inexpensive, and poses little threat to the environment or human health in the amounts used as a SCF or a SBCF (e.g., as SCCO2 or SBCCO2). Other fluids that are capable of use as a SCF or SBCF in various applications include methane, ethane, propane, argon, nitrous oxide and water. These fluids have been utilized as supercritical fluids for applications as diverse as extraction, inorganic/organic synthesis, catalysis, material processing, and even dry-cleaning.
It is desired to utilize densified fluid technology to impregnate a substrate, e.g., with one or more drug compounds.